This invention provides compounds of the formula (I): ##STR00001##
wherein Y.sup.1, Y.sup.2, Z, X.sup.1, X.sup.2, and W are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and PI3K/AKT/mTor signaling pathway kinases-mediated diseases or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3-ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROS1; MAPK pathway kinases selected from ARAF, BRAF, CRAF, ERK1/2, MEK1, MEK2, MEK3, MEK4, MEK5, MEK6, and MEK7; and PI3K/AKT/mTor pathway kinases: selected from mTor, PI3K , PI3K , PI3K , and PI3K .

This invention provides compounds of the formula (I): ##STR00001##
wherein Y.sup.1, Y.sup.2, Z, X.sup.1, X.sup.2, and W are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and PI3K/AKT/mTor signaling pathway kinases-mediated diseases or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3-ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROS1; MAPK pathway kinases selected from ARAF, BRAF, CRAF, ERK1/2, MEK1, MEK2, MEK3, MEK4, MEK5, MEK6, and MEK7; and PI3K/AKT/mTor pathway kinases: selected from mTor, PI3K , PI3K , PI3K , and PI3K .

Disclosed are halo substituted derivative compounds of sobetirome with improved pharmacological characteristics relative to sobetirome, pharmaceutical compositions that include those compounds and methods of treating diseases such as neurodegenerative disorders using those pharmaceutical compositions.

Disclosed are halo substituted derivative compounds of sobetirome with improved pharmacological characteristics relative to sobetirome, pharmaceutical compositions that include those compounds and methods of treating diseases such as neurodegenerative disorders using those pharmaceutical compositions.

The present invention relates to the compounds of formula (I) below:

##STR00001##

wherein: X represents an oxygen atom, a sulfur atom, a nitrogen atom or a CH radical, The bond XY and Y are absent if X represents an oxygen or sulfur atom, the bond XY and Y are present if X represents a nitrogen atom or a CH radical, When present, Y represents a group R if X represents a nitrogen atom, a hydrogen atom or a group NR.sup.1R.sup.2 if X represents a CH radical, (Het)Ar is an aromatic ring selected from the group consisting of aryl and heteroaryl groups, R.sup.3, R.sup.4, R.sup.5, R.sup.6 represent, independently of one another, a hydrogen atom, a halogen atom, a NR.sup.12R.sup.13, a SR.sup.14 group, a OR.sup.14 group or a CF.sub.3 group, When Y is NR.sup.1R.sup.2, the groups NR.sup.1R.sup.2 and (Het)Ar are in the cis-conformation,
or a pharmaceutically acceptable salt thereof,
for use in the treatment of proliferative diseases, infectious diseases, allergies, inflammation and/or asthma.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species.

Also disclosed is a fluorination method comprising providing , a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species.

Further disclosed a fluorination method comprising providing a compound having the structure Ar-OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar-OH to provide a fluorinated aryl species having the structure Ar-F.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species.

Also disclosed is a fluorination method comprising providing , a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species.

Further disclosed a fluorination method comprising providing a compound having the structure Ar-OH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure Ar-OH to provide a fluorinated aryl species having the structure Ar-F.

A crosslinking agent includes a compound represented by the following formula (1). ##STR00001##
wherein R.sup.1, R.sup.2, and R.sup.3 are independently a hydrogen atom, a fluorine atom, an alkyl group, a fluoroalkyl group, or a substituted or unsubstituted aryl group, a plurality of R.sup.1 are identical to or different from each other, a plurality of R.sup.2 are identical to or different from each other, a plurality of R.sup.3 are identical to or different from each other, provided that at least one of R.sup.1, R.sup.2, and R.sup.3 is a hydrogen atom, and at least one of R.sup.1, R.sup.2, and R.sup.3 is a fluorine atom or a fluorine atom-containing group, m is an integer from 2 to 6, l is an integer from 0 to 2, and each hydrogen on the benzene ring(s) may be substituted.

A crosslinking agent includes a compound represented by the following formula (1). ##STR00001##
wherein R.sup.1, R.sup.2, and R.sup.3 are independently a hydrogen atom, a fluorine atom, an alkyl group, a fluoroalkyl group, or a substituted or unsubstituted aryl group, a plurality of R.sup.1 are identical to or different from each other, a plurality of R.sup.2 are identical to or different from each other, a plurality of R.sup.3 are identical to or different from each other, provided that at least one of R.sup.1, R.sup.2, and R.sup.3 is a hydrogen atom, and at least one of R.sup.1, R.sup.2, and R.sup.3 is a fluorine atom or a fluorine atom-containing group, m is an integer from 2 to 6, l is an integer from 0 to 2, and each hydrogen on the benzene ring(s) may be substituted.

The present disclosure relates to HIF-2 inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2 scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.